1. Field of the Invention
The present invention is directed to a composition and method useful in preparing peptides and, more particularly, in the industrial synthesis of aspartyl peptides such as sweetening agents or polypeptide hormones.
2. Description of the Prior Art
It is well known that preparation of aspartyl peptides is especially difficult because aspartic acid has two non-identical acid functions. For example, the mixed anhydride of benzyloxycarbonyl aspartic acid, which is the accustomed intermediate for synthesis of these peptides, results in a mixture of .alpha. and .beta. aspartyl peptides, which is difficult to separate causing a reduction in the yield of the desired isomer.
To avoid formation of the non-desired isomer, certain methods in the literature have described use of aspartic acid derivatives with two protecting groups, one on the nitrogen and one on a selected acid function of the aspartic acid. For example, a combination of protecting groups in which the .beta.-carboxyl group is converted to the .beta.-benzyl ester, and the nitrogen is protected with benzyloxycarbonyl was described by Bryant, Journal of the Chemical Society, 1959, p. 3868 and by German Pat. No. 2.608.174. However, industrial peptide syntheses involving an aspartic acid intermediate having the foregoing protecting groups has proven impractical due to the length of time needed to prepare the intermediate, the cost of the raw materials (lithium hydroxide and benzyl chloroformate) and the problems arising from de-protection of the desired peptides. For example, hydrogenolysis of the two benzyl protections liberates toluene which impedes further hydrogenolysis by coating the catalyst.